TOF and M-TOF:
Time-of-flight mass spectrometers (TOF MS) are widely used in analytical chemistry for identification and quantitative analysis of various mixtures. Sensitivity and resolution of such analysis is an important concern for practical use. To increase resolution of TOF MS, U.S. Pat. No. 4,072,862 by Mamyrin et al, incorporated herein by reference, discloses an ion mirror for improving time-of-flight focusing in respect to ion energy. To increase sensitivity of TOF MS, WO9103071 by Dodonov et al, incorporated herein by reference, discloses a scheme of orthogonal pulsed injection providing efficient conversion of continuous ion flows into pulsed ion packets. It has been long recognized that the resolution of TOF MS scales with the flight path.
To raise the flight path while keeping moderate physical length, there have been suggested multi-pass time-of-flight mass spectrometers (M-TOF MS) including multi-reflecting (MR-TOF) and multi-turn (MT-TOF) mass spectrometers. SU1725289 by Nazarenko et al, incorporated herein by reference, introduces a scheme of a folded path MR-TOF MS using two-dimensional gridless and planar ion mirrors (FIG. 1). Mirror geometry and potentials are arranged to provide isochronous ion oscillations. Ions experience multiple reflections between planar mirrors, while slowly drifting towards the detector in a so-called shift direction (here Z-axis). The number of cycles and the resolution are adjusted by varying an ion injection angle. However, by principle of time-of-flight detection, the technique assumes a fixed flight path, and the number of ion reflections is limited to few to avoid overlaps between adjacent reflections.
GB2403063 and U.S. Pat. No. 5,017,780, incorporated herein by reference, disclose a set of periodic lenses within the two-dimensional MR-TOF to confine ion packets along the main zigzag trajectory. The scheme provides fixed ion path and allows using many tens of ion reflections without spatial overlapping. However, the use of periodic lenses inevitably causes time-of-flight aberrations which forces to limit the spatial size of ion packets. WO2007044696, incorporated herein by reference, suggests a scheme with double orthogonal injection in order to increase the efficiency of ion pulsed injection into planar MR-TOF. In spite of the improvement, the duty cycle of the pulsed conversion still remains under 1%. Velocity modulation within a gaseous radiofrequency (RF) ion guide prior to orthogonal acceleration improves the duty cycle by 5-10-fold.
Kozlov et al in the paper “Space Charge Effects in Multi-reflecting Time-of-flight Mass Spectrometer”, Proc. of 54th ASMS Conference on Mass Spectrometry, May, 2006, Seattle, incorporated herein by reference, describe the use of an axial trap for ion accumulation and pulsed injection into an MR-TOF. The scheme improves the duty cycle to almost a unity and allows passing compact ion packets into MR-TOF analyzers. However, due to space charge effects, both the trap and MR-TOF analyzer rapidly saturate at ion fluxes above 1E+6 to 1E+7 ions/second (i/s). This is much smaller than can be delivered by modern ion sources providing up to 1E+9 i/s in case of ESI, PI and APCI sources, up to 1E+10 i/s in case of EI sources and up to 1E+11 i/s in case of ICP ion sources. Space charge saturation does limit the dynamic range of LC-MS and LC-MS-MS analysis, particularly when high speed of data acquisition (>10 spectra per second) is required.
Summarizing the above, the MR-TOF mass spectrometers of the prior art enhance the resolution but have limited duty cycle (and hence sensitivity) and limited dynamic range, since they cannot accept large ion flows above 1E+7 i/s from modern ion sources without degrading the analyzer parameters.
E-Trap MS with a TOF Detector:
In this hybrid—E-Trap/TOF technique, ions are pulsed injected into a trapping electrostatic field and experience repetitive oscillations along the same ion path. After some delay corresponding to a large number of cycles, ion packets are pulsed ejected onto the TOF detector. In FIG. 5 of GB2080021 and in U.S. Pat. No. 5,017,780, incorporated herein by reference, ion packets are reflected between coaxial gridless mirrors. Since ions repeat the same axial trajectory the scheme is called I-path M-TOF. Another type of hybrid M-TOF/E-trap is implemented within a multi-turn MT-TOF with electrostatic sectors. Looping of ion trajectories between electrostatic sectors is described by Ishihara et al in U.S. Pat. No. 6,300,625 and in “A Compact Sector-Type Multi-Turn Time-of-Flight Mass Spectrometer MULTUM-2”, Nuclear Instruments and Methods Phys. Res., A 519 (2004) 331-337, incorporated herein by reference. In all hybrid E-Trap/TOF methods, to avoid spectral overlaps, the analyzed mass range is shrunk reverse proportional to number of cycles.
E-Trap MS with Frequency Detector:
To overcome mass range limitations the I-path M-TOF has been converted into I-path electrostatic traps in which ion packets are not ejected onto a detector, but rather an image current detector is employed to sense the frequency of ion oscillations as suggested in U.S. Pat. No. 6,013,913A, U.S. Pat. No. 5,880,466, and U.S. Pat. No. 6,744,042, incorporated herein by reference. Such systems are referred as I-path E-traps or Fourier Transform (FT) I-path E-traps. The I-path E-traps suffer slow oscillation frequency and very limited space charge capacity. A combination of low oscillation frequencies (under 100 kHz for 1000 amu ions) and low space charge capacity (1E+4 ions per injection) either severely limit an acceptable ion flux or lead to strong space charge effects, such as self-bunching of ion packets and peaks coalescence.
In U.S. Pat. No. 5,886,346, incorporated herein by reference, Makarov suggested electrostatic Orbital Trap with an image charge detector (trade mark ‘Orbitrap’). The Orbital Trap is a cylindrical electrostatic trap with a hyper-logarithmic field. Pulsed injected ion packets rotate around the central spindle electrode in order to confine ions in the radial direction, and oscillate in a nearly ideal linear field (quadratic potential distribution) which provides harmonic axial ion oscillations with the period being independent on the ion energy. An image charge detector senses the frequency of ion axial oscillations. The combination of Orbitrap with so-called C-trap (RF linear trap with curved axis and with radial ion ejection) provides a larger space charge capacity (SCC) per single ion injection: SCC=3E+6 ions/injection (Makarov et al, “Performance Evaluation of a High-Field Orbitrap Mass Analyzer” JASMS., v. 20 (2009) #8, pp 13911396, incorporated herein by reference). However, the orbital trap suffers slow signal acquisition. The signal acquisition with the image detector takes about 1 second for obtaining spectra with 100,000 resolution at m/z=1000. The slow acquisition speed in combination with space charge limit of the C-trap do limit the duty cycle of mass spectrometer to 0.3% in most unfavorable cases.
Thus, in the attempt of reaching high resolving power, the prior art multi-pass time-of-flight mass spectrometers and electrostatic traps with an image charge detection do limit the accepted ion flux under 1E+7 i/s which limits the effective duty-cycle under 0.3-1% in most unfavorable cases.
It is an object of at least one aspect of the present invention to obviate or mitigate at least one or more of the aforementioned problems.
It is a further object of at least one aspect of the present invention to improve the ion flux throughput and the duty cycle of mass spectrometers with high resolving power in the range of about 100,000.